Search

Pembrolizumab, a programmed death 1 ligand (PD‐1) checkpoint inhibitor, has elicited responses in mismatch repair (MMR)–deficient advanced solid tumors, leading to its agnostic approval by the US Food and Drug Administration in 2017 when no other therapeutic options are available. However, there are still insufficient data on the response to checkpoint inhibitors in advanced endometrial cancer related to Lynch syndrome (LS) and, specifically, in uterine serous carcinoma, which is uncommon in LS. Here we report a case of metastatic uterine serous carcinoma due to a germline MSH6 mutation (Lynch syndrome) that was discovered because of a patient's tumor MMR deficiency. The patient was started on first‐line pembrolizumab in 2018 and sustained a partial response. She remains asymptomatic and progression free for more than 2 years. Tumor sequencing showed a high mutational burden and an upstream somatic mutation in the same gene, p.F1088fs. Immunohistochemical staining was negative for PD‐L1 expression. We discuss clinical characteristics of the patient, molecular features of her tumor, and the mechanism of her tumor response. We also discuss the duration of immunotherapy in her case. Our case demonstrated a partial response and a long‐term remission from the frontline single‐agent pembrolizumab in a woman with metastatic uterine serous carcinoma and Lynch syndrome due to a germline MSH6 gene mutation. Our experience suggests a potential significant clinical benefit of checkpoint inhibitors used as single agents early on in the treatment of MMR‐deficient/high microsatellite instability/hypermutated uterine cancers in women with Lynch syndrome. Key Points: Even though checkpoint inhibitors are effective in mismatch repair‐deficient endometrial cancer, it is unknown whether the response to them differs between women with endometrial cancer due to germline mutations in a mismatch repair gene (Lynch syndrome) and women with sporadic endometrial cancer.In our case, a patient with Lynch syndrome and recurrent mismatch repair‐deficient serous endometrial cancer achieved a durable remission on the first‐line therapy with the checkpoint inhibitor pembrolizumab and remains progression free after more than 2 years.Based on our observation and the data, suggesting the stronger immune activation in women with Lynch syndrome–associated endometrial cancer, we propose to use checkpoint inhibitor monotherapy early in the course of their treatment and stratify patients for the presence of Lynch syndrome in clinical trials. This case report describes a partial response and a long‐term remission from the front‐line single‐agent pembrolizumab in a patient with metastatic uterine serous carcinoma and Lynch syndrome due to a germline MSH6 gene mutation, suggesting a potential significant clinical benefit of checkpoint inhibitors used as single agents early on in the treatment of uterine cancers in women with Lynch syndrome. [ABSTRACT FROM AUTHOR]

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

We present new precision measurements of the elastic electron-proton scattering cross section for momentum transfer (Q^{2}) up to 15.75  (GeV/c)^{2}. Combined with existing data, these provide an improved extraction of the proton magnetic form factor at high Q^{2} and double the range over which a longitudinal or transverse separation of the cross section can be performed. The difference between our results and polarization data agrees with that observed at lower Q^{2} and attributed to hard two-photon exchange (TPE) effects, extending to 8  (GeV/c)^{2} the range of Q^{2} for which a discrepancy is established at >95% confidence. We use the discrepancy to quantify the size of TPE contributions needed to explain the cross section at high Q^{2}.

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4  GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

A trial of a bile acid binder such as cholestyramine or colestipol may benefit patients with postcholecystectomy diarrhea.